Obesity is a health crisis of epic proportions. About 34% of adults in the US have obesity, up from 31 % in 1999 and about 15% in the years 1960 to 1980. The chronic diseases that result from obesity annually cost over $150 billion in weight-related medical bills. Reduction of obesity improves cardiovascular and other health outcomes, yet what is currently known about obesity is inadequate to combat the global obesity epidemic. A comprehensive understanding about the mechanics of obesity may help in developing more effective preventive and treatment strategies, which in turn will substantially improve cardiovascular and other health measures.

Feasibility and challenges of addressing this CQ or CC:

Years of obesity research have revealed the complex nature of this disease and its multi-factorial etiology. While research has firmly established the role of energy balance in weight gain and weight loss, it is important to discover upstream factors that predispose only certain individuals to energy imbalance. This may be addressed by further focusing on newly identified putative contributors of obesity, including but not limited to the impact of sleep deprivation, ambient temperature, age at first pregnancy, intrauterine and intergenerational factors, neuro-endocrine factors, epigenetics, environmental chemicals and endocrine disruptors, gut microbes, infections and the immune system, and social and behavioral factors associated with obesogenic behaviors. These studies may provide mechanistic insight that may also lead to the development of new pharmacological approaches. It is possible that cause-specific prevention or treatment approaches may yield more effective results than generic approaches that do not necessarily consider upstream modulators of energy imbalance, or inter-individual differences.

Name of idea submitter and other team members who worked on this idea:
The Obesity Society

Past research focused on using variations of diet and exercise has revealed important information about the health benefits of weight loss. The limitations of such approaches in producing biologically meaningful and sustained weight loss for the majority have also been recognized. Even within a study population, compliance to weight loss regimen, weight loss and its sustainability, and improvement in health outcomes vary considerably. Research is needed to identify the basis for this variation, which may lead to enhanced outcome and applicability of such approaches.

Feasibility and challenges of addressing this CQ or CC:

Identifying factors that enhance weight management response may lead to translational studies that yield more effective results. A strong support of promising clinical translational research may promote a conducive environment for developing more practical applications.

Name of idea submitter and other team members who worked on this idea:
The Obesity Society

Population based and epidemiological studies have identified segments of population that are resistant or susceptible to obesity and cardiovascular risks. Continued research is needed to identify additional such populations and their differences. Moreover, the next phase of research could be to understand the basis for this relative resistance or vulnerabilities, and exploit the information to improve obesity and cardiovascular disease risk at a community level.

Feasibility and challenges of addressing this CQ or CC:

Moving forward, strategies are needed that don’t yield only incremental benefits, but instead emphasize ‘high risk, high impact’ research to some extent. Given the enormous public health crisis obesity represents we urge continued support of basic, clinical, population, and translational obesity research.

Name of idea submitter and other team members who worked on this idea:
The Obesity Society

Voting

Self-report data indicate that insufficient sleep is more common in minority populations. This seems to be related to socioeconomic status. There is a need to move this beyond self-report and obtain objective measures in the relevant populations. Moreover, the basis of this difference needs to be established. What aspect of the environment leads to these differences, e.g., noise, stress related to sense of vulnerability,
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Self-report indicates that sleep duration is lower in minority populations. This seems to be related to socioeconomic groups. To address this issue requires understanding the basis of this and developing appropriate interventions.

The impact of this is as follows:

a. Implementing new technology based on mobile approaches to assess sleep duration in subjects in different socioeconomic groups.

b. Developing a comprehensive approach to understanding and evaluating environmental influences in sleep and circadian rhythm.

There is rapidly developing new mobile technology to assess sleep duration and other phenotypes in individuals living in their normal lives. There are a number of studies currently being conducted that could be leveraged to address this question. There are also developing approaches to assess environmental influences on sleep and circadian rhythm such as noise, light exposure, etc. Thus, this question could be addressed in the near future.

Name of idea submitter and other team members who worked on this idea:
Sleep Research Society

Voting

Studies in different subjects have shown that there are major individual differences in response to sleep loss and circadian disruption. Twin studies have shown that this is heritable. There needs to be an intensive effort to assess basis of these individual differences. This could include in-depth phenotyping studies, e.g., neuroimaging, genetic studies, “-omic” studies, epigenetic changes, etc.

There are major individual differences in response to sleep loss (both acute and chronic) and to circadian disruption. This has major impact both in terms of health consequences and in safety. Some individuals are particularly vulnerable to sleep loss and hence are more likely to have adverse consequences of losing sleep—increased risk of crashes, errors by physicians, etc. They are also more likely to be affected by metabolic and other consequences if they have chronic insufficient sleep.

Identifying the basis of these individual differences will have several impacts:

1. It will provide likely targets for development of biomarkers to assess effect of sleep loss and circadian disruption.

2. It will provide tools to risk stratify individuals and to employ preventative strategies to reduce risk of major adverse consequences.

3. It will identify novel pathways that could be the target for future intervention studies.

Feasibility and challenges of addressing this CQ or CC:

These studies are highly feasible. Phenotyping and recruitment strategies to study this question have been established in many laboratories. Moreover, more laboratories are utilizing genetic, -omic approaches and epigenetic approaches that could be applied to this question. There is also a developing repertoire of neuroimaging studies that can be applied to address this question.

Name of idea submitter and other team members who worked on this idea:
Sleep Research Society

Voting

There are developing data from clinical studies that sleep deficiency and circadian disruption have multiple adverse consequences for health. The clinical data provide the base for mechanistic studies. Studies in animal models indicate that both circadian disruption and insufficient sleep later gene expression in peripheral tissues. Moreover, the effect of sleep loss in molecular changes in brain changes with age.
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There is no doubt that insufficient sleep and circadian disruption are very common in our society. There are also compelling epidemiological data that they are associated with multiple adverse consequences, including increased cardiovascular disease, increase in metabolic abnormalities such as insulin resistance and for shift work an increased incidence of specific concern. Animal studies based on microarrays are showing that inadequate sleep and circadian rhythm alter gene expression not only in brain but also in peripheral tissues. These studies are hypothesis-generating and there are many opportunities for hypothesis-driven research in this area to assess mechanisms. Identifying mechanisms will allow investigators to begin to assess mechanisms of individual differences and to identify new pathways for intervention.

Feasibility and challenges of addressing this CQ or CC:

Sleep and circadian research is in a very strong position. Sleep and clock function has now been identified in all the major model systems—C. elegans, Aphysia, Drosophila, zebra-fish, mice, etc. Thus, there is a strong platform to assess conserved pathways for effect of sleep loss and circadian disruption. Moreover, microarray studies have identified likely pathways thereby setting up hypothesis-driven research. There are major opportunities in this area.

Name of idea submitter and other team members who worked on this idea:
Sleep Research Society

A whole blood donation rapidly removes approximately 10% of total blood volume within about 15 minutes, providing a unique opportunity to examine how biochemical pathways regulating iron metabolism and hemoglobin biosynthesis respond to acute hemorrhage in otherwise healthy individuals. Genetic studies could examine the impact of polymorphisms of iron regulatory and hemoglobin biosynthesis proteins on the physiological responses to blood donation and recovery from blood donation or to identify previously unrecognized polymorphisms and proteins that affect dietary iron absorption and hemoglobin synthesis. Blood donor diversity might enable research into the genetic determinants of the racial variability in hemoglobin set point or the changes in biochemical responses with aging. The results of basic studies in healthy individuals may also help to understand disease mechanisms and treatments for anemia, inflammation, iron overload, bone marrow expansion/bone health, infectious diseases, neurological disorders and cancer.

Feasibility and challenges of addressing this CQ or CC:

Blood donors are often willing to participate in research studies, especially when study design allows completion in one donor visit. More complex studies requiring donor follow-up or an intervention can also be rapidly enrolled and completed based on past experience. Clinical assays to measure iron regulatory proteins are currently available and tools for complex genetic analyses are rapidly advancing. Thus, the likelihood of completing study enrollment and answering specific questions about responses of iron metabolism proteins to blood donation in a time period of 3-10 years is high.

Name of idea submitter and other team members who worked on this idea:
Dana Devine PhD and Anne Eder MD PhD for the 2015 NHLBI State of the Science in Transfusion Medicine

Weight loss has health benefits in diabetes reduction, risk factor improvement, improvement in symptoms of sleep apnea, improvement in NAFLD, improvement in feeling and function (knee pain, urinary stress incontinence, sexual function). In all these circumstances, greater weight loss yields more benefit. Our best lifestyle interventions, delivered by the most skilled behaviorists yield weight loss of, on average 8% and one third of persons undergoing the intervention do not lose even 5%. How can we use multiple approaches together to improve the amount and durability of weight loss achieved in our counseling programs.

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.